1. Field of the Invention
The present invention is in the field of devices used to subject portions of a blood vessel to nuclear radiation to prevent restenosis of the irradiated area after performance of an angioplasty procedure.
2. Background Information
A common problem after performance of a percutaneous transluminal coronary angioplasty is the restenosis of the treated area. In fact, restenosis occurs in 30% to 50% of cases. Restenosis occurs, at least in part, as a result of vascular smooth muscle cell migration, proliferation, and neointima formation at the site of the angioplasty. It has been shown that intracoronary delivery of ionizing radiation causes focal medial fibrosis, which when delivered at the site of the angioplasty, impedes the restenosis process. Adjacent coronary segments and the surrounding myocardium are undamaged by the irradiation treatment.
Delivery of the ionizing radiation at the site of the stenosis can be achieved by the introduction of an irradiation source, such as a ribbon, through an infusion catheter. In such systems, the infusion catheter is inserted to the site of the stenosis over a guidewire which may be inserted before, or alternatively, left after, the performance of an angioplasty procedure. After insertion of the infusion catheter, the guidewire is usually removed from the catheter, and the irradiation ribbon is inserted in its place. The irradiation ribbon typically incorporates a plurality of Iridium-192 seeds or pellets near its distal end. This plurality of radioactive sources arranged essentially in a line approximates a line source, although the intensity of the radiation will vary axially to some extent, depending upon the spacing and length of the seeds. Other sources that might not be line sources of ionizing radiation can be used, as well.
Such systems have several disadvantages. First, location of the radioactive material radially within the blood vessel is often uncontrolled. Rotation of the infusion catheter may assist in centering the radiation source within the stenosis, in some cases, but this method is not always effective. Centering of the radioactive material within the tissues injured by the angioplasty may be required, because it is important to deliver a known dose of radiation uniformly to the affected tissue. The intensity of gamma or beta radiation emanating from a source varies inversely with the square of the radial distance from the source. Therefore, if the radiation source is not centered within the blood vessel, the dose delivered to one side of the vessel can vary greatly from the dose delivered to the opposite side. In addition, if the line source lies at an angle to the centerline of the vessel, rather than being concentric therewith, or at least parallel thereto, the dose delivered can vary axially by an appreciable amount, throughout the length of the stenosis.
A second disadvantage of known systems is that dosimetry is often inaccurate. Proper dosimetry is essential for effective treatment of vascular disease with radiation therapy. There are two general classifications of radiation sources used in these applications, gamma and beta. Gamma radiation is highly penetrating and can act at a relatively far distance from the source. Beta radiation, however, penetrates very weakly and will only adequately treat tissue approximately 2 or 3 mm. away from the source. Beta radiation is also easily shielded by metals and thick plastics. One of the advantages of beta radiation over gamma radiation is less general radiation exposure to the patient and attending health care personnel. The disadvantage of beta radiation is the difficulty in getting an adequate dose delivered to the intended target, because the dose drops off so quickly with distance. The advantages of gamma radiation are excellent penetration, providing favorable dosimetry. The disadvantages of gamma radiation are increased exposure to the patient and the hospital personnel.
Animal and human studies have shown that a dose of approximately 800 to 3000 cGy will be effective at inhibiting the proliferation of vascular disease. The challenge is delivering this dose to the vessel wall segments responsible for the proliferation process, without delivering too high a dose to the innermost layers of the vessel wall. Too high a dose delivered to the inner layers of the vessel wall could create a weakening of the wall, leading to perforation and/or accelerated disease.
Recently, excellent dosimetry to treat vascular disease has been demonstrated using a radioactive liquid filled balloon. Radioactive isotopes such as Re-188 penetrate approximately 3 mm. from the source. When delivered through a liquid filled balloon system, the radioactive isotope is mixed in the balloon and is held up against the vessel wall by the balloon. Therefore, the radioactive isotope is brought to the vessel wall so that its approximate 3 mm. penetration is from the edge of the balloon catheter. This has advantages over the more traditional wire-based beta sources where the approximate 3 mm. penetration is measured from a wire located within a delivery catheter, which is placed at or near the center of the vessel lumen. Additionally, since the radioactive source is mixed homogeneously in the balloon, the vessel is, in essence, exposed to multiple radioactive sources distributed throughout the balloon, some directly against the vessel wall and others more toward the center of the vessel.
One of the disadvantages of a liquid filled balloon is that the balloon will always have a finite rate of breakage. A broken balloon will lead to radioactive materials contaminating the human circulatory system which could have adverse, unwanted side effects. Furthermore, when the balloon is deflated, most of the radioactivity is withdrawn into a shielded housing, such as a large syringe or bladder; however, some small amount of radioactivity remains within the balloon and in the catheter connecting the balloon to the shielded storage housing. The physician/operator must remove the balloon catheter from the patient's body, which will, of necessity, require placing his or her hands on the catheter. Though the catheter contains only a small amount of radioactivity, there is a potential for unwanted operator exposure. Finally, some liquid filled balloon catheter systems require the operator to fill and prepare the balloon in the cardiac catheterization laboratory. This opens the possibility of contamination due to unintentional spillage by the operator, as the system is prepared and filled.
It is an object of the present invention to provide a catheter assembly for irradiation of a stenotic segment of a blood vessel, which can place an expandable irradiation source at a desired location within a blood vessel, and expand the source to contact, or nearly contact, the blood vessel wall. It is a further object of the present invention to provide an irradiation catheter assembly with an expandable source, which avoids the risk of releasing radiation into the bloodstream, which minimizes operator exposure, and which avoids the risk of contamination of the catheterization laboratory. Finally, it is an object of the present invention to provide a catheter assembly which is economical to manufacture and easy to use.